Tetrahydrobiopterin rapidly reduces the SOD mimic Mn(III) ortho-tetrakis(N-ethylpyridinium-2-yl)porphyrin.

Abstract

Mn(III) ortho-tetrakis(N-ethylpyridinium-2-yl)porphyrin (Mn(III)TE-2-PyP(5+)) effectively scavenges reactive oxygen and nitrogen species in vitro, and protects in vivo, in different rodent models of oxidative stress injuries. Further, Mn(III)TE-2-PyP(5+) was shown to be readily reduced by cellular reductants such as ascorbic acid and glutathione. We now show that tetrahydrobiopterin (BH(4)) is also able to reduce the metal center. Under anaerobic conditions, in phosphate-buffered saline (pH 7.4) at 25 +/- 0.1 degrees C, reduction of Mn(III)TE-2-PyP(5+) occurs through two reaction steps with rate constants k(1) = 1.0 x 10(4) M(-1) s(-1) and k(2) = 1.5 x 10(3) M(-1) s(-1). We ascribe these steps to the formation of tetrahydrobiopterin radical (BH(4)(.+)) (k(1)) that then undergoes oxidation to 6,7-dihydro-8H-biopterin (k(2)), which upon rearrangement gives rise to 7,8-dihydrobiopterin (7,8-BH(2)). Under aerobic conditions, Mn(III)TE-2-PyP(5+) catalytically oxidizes BH(4). This is also true for its longer chain alkyl analog, Mn(III) ortho-tetrakis(N-n-octylpyridinium-2-yl)porphyrin. The reduced Mn(II) porphyrin cannot be oxidized by 7,8-BH(2) or by l-sepiapterin. The data are discussed with regard to the possible impact of the interaction of Mn(III)TE-2-PyP(5+) with BH(4) on endothelial cell proliferation and hence on tumor antiangiogenesis via inhibition of nitric oxide synthase.

• Authors: Ines Batinić-Haberle, Ivan Spasojević, Irwin Fridovich
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 37 Issue 3 Pg. 367-74 (Aug 01 2004) ISSN: 0891-5849 [Print] United States
• PMID: 15223070 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Metalloporphyrins
• Reducing Agents
• manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin
• Biopterin
• Superoxide Dismutase
• sapropterin
• Oxygen

Topics

• Biopterin (analogs & derivatives, chemistry)
• Kinetics
• Metalloporphyrins (chemistry)
• Molecular Structure
• Oxidation-Reduction
• Oxygen (chemistry, metabolism)
• Reducing Agents (chemistry)
• Spectrophotometry, Ultraviolet
• Superoxide Dismutase (chemistry)